ClinVar Miner

Submissions for variant NM_002180.3(IGHMBP2):c.1060+8G>T

gnomAD frequency: 0.00076  dbSNP: rs201147313
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000725441 SCV000336957 uncertain significance not provided 2015-11-06 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000398567 SCV000373773 uncertain significance Autosomal recessive distal spinal muscular atrophy 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000341120 SCV000519004 likely benign not specified 2018-01-29 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV001080208 SCV000642293 likely benign Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S 2024-01-29 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory, London Health Sciences Centre RCV001174191 SCV001337317 likely benign Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000725441 SCV001472841 likely benign not provided 2020-04-04 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000725441 SCV001500978 uncertain significance not provided 2021-09-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000341120 SCV002500218 likely benign not specified 2022-03-08 criteria provided, single submitter clinical testing Variant summary: IGHMBP2 c.1060+8G>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant no significant impact on splicing. Three predict the variant creates an alternate intronic 5' splice donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0006 in 251294 control chromosomes. This frequency does not allow conclusions about variant significance. To our knowledge, no occurrence of c.1060+8G>T in individuals affected with Charcot-Marie-Tooth Disease, Axonal, Type 2S and no experimental evidence demonstrating its impact on protein function have been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (likely benign, n=3; VUS, n=3). Based on the evidence outlined above, the variant was classified as likely benign.

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